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Molecules (Basel, Switzerland) Jun 2018Diterpenes have been identified as active compounds in several medicinal plants showing remarkable biological activities, and some isolated diterpenes are produced at... (Review)
Review
Diterpenes have been identified as active compounds in several medicinal plants showing remarkable biological activities, and some isolated diterpenes are produced at commercial scale to be used as medicines, food additives, in the synthesis of fragrances, or in agriculture. There is great interest in developing methods to obtain derivatives of these compounds, and biotransformation processes are interesting tools for the structural modification of natural products with complex chemical structures. Biotransformation processes also have a crucial role in drug development and/or optimization. The understanding of the metabolic pathways for both phase I and II biotransformation of new drug candidates is mandatory for toxicity and efficacy evaluation and part of preclinical studies. This review presents an overview of biotransformation processes of diterpenes carried out by microorganisms, plant cell cultures, animal and human liver microsomes, and rats, chickens, and swine in vivo and highlights the main enzymatic reactions involved in these processes and the role of diterpenes that may be effectively exploited by other fields.
Topics: Animals; Biotransformation; Diterpenes; Humans; Molecular Structure
PubMed: 29890639
DOI: 10.3390/molecules23061387 -
Molecules (Basel, Switzerland) Dec 2021(Lamiaceae), which-according to the latest systematic revision-includes three separate genera (, , and ), is a genus widely used in traditional medicine-mainly in the... (Meta-Analysis)
Meta-Analysis Review
(Lamiaceae), which-according to the latest systematic revision-includes three separate genera (, , and ), is a genus widely used in traditional medicine-mainly in the treatment of various ailments of the digestive tract, respiratory tract, and skin. Many species of have been shown to produce phenolic compounds and terpenes. Diterpenes, especially those of the abietane class, are the most studied group of secondary metabolites found in , which is characterized by a significant structural diversity arising from the oxygenation and further rearrangement of the basic tricyclic abietane skeleton to a complete aromatization of the ring system. This review summarizes the known information on abietane diterpenes, showing their structures, sources, and biosynthesis. A classification of these compounds into nine groups, according to the arrangement of their ring C, is used. Royleanones, spirocoleons, and hydroquinones are the largest classes of abietane diterpenes, covering more than 70% of all the compounds reviewed.
Topics: Abietanes; Diterpenes; Molecular Structure; Phytochemicals; Plant Extracts; Plectranthus; Structure-Activity Relationship
PubMed: 35011401
DOI: 10.3390/molecules27010166 -
Molecules (Basel, Switzerland) Nov 2022Marine-derived fungi are important sources of novel compounds and pharmacologically active metabolites. As an important class of natural products, diterpenes show... (Review)
Review
Marine-derived fungi are important sources of novel compounds and pharmacologically active metabolites. As an important class of natural products, diterpenes show various biological activities, such as antiviral, antibacterial, anti-inflammatory, antimalarial, and cytotoxic activities. Developments of equipment for the deep-sea sample collection allow discoveries of more marine-derived fungi with increasing diversity, and much progress has been made in the identification of diterpenes with novel structures and bioactivities from marine fungi in the past decade. The present review article summarized the chemical structures, producing organisms and biological activities of 237 diterpenes which were isolated from various marine-derived fungi over the period from 2009 to 2021. This review is beneficial for the exploration of marine-derived fungi as promising sources of bioactive diterpenes.
Topics: Fungi; Biological Products; Diterpenes; Antimalarials; Anti-Bacterial Agents; Aquatic Organisms
PubMed: 36500394
DOI: 10.3390/molecules27238303 -
Toxins May 2019Indole-diterpenes are an important class of chemical compounds which can be unique to different fungal species. The highly complex lolitrem compounds are confined to... (Review)
Review
Indole-diterpenes are an important class of chemical compounds which can be unique to different fungal species. The highly complex lolitrem compounds are confined to species, whilst penitrem production is confined to spp. and spp. These fungal species are often present in association with pasture grasses, and the indole-diterpenes produced may cause toxicity in grazing animals. In this review, we highlight the unique structural variations of indole-diterpenes that are characterised into subgroups, including paspaline, paxilline, shearinines, paspalitrems, terpendoles, penitrems, lolitrems, janthitrems, and sulpinines. A detailed description of the unique biological activities has been documented where even structurally related compounds have displayed unique biological activities. Indole-diterpene production has been reported in two classes of ascomycete fungi, namely Eurotiomycetes (e.g., and ) and Sordariomycetes (e.g., and ). These compounds all have a common structural core comprised of a cyclic diterpene skeleton derived from geranylgeranyl diphosphate (GGPP) and an indole moiety derived from tryptophan. Structure diversity is generated from the enzymatic conversion of different sites on the basic indole-diterpene structure. This review highlights the wide-ranging biological versatility presented by the indole-diterpene group of compounds and their role in an agricultural and pharmaceutical setting.
Topics: Animals; Diterpenes; Endophytes; Humans; Indoles; Mycotoxins; Poaceae; Tremor
PubMed: 31137882
DOI: 10.3390/toxins11050302 -
Applied Microbiology and Biotechnology Feb 2019Indole-diterpenes (IDTs) such as the aflatrems, janthitrems, lolitrems, paspalitrems, penitrems, shearinines, sulpinines, and terpendoles are biogenetically related but... (Review)
Review
Indole-diterpenes (IDTs) such as the aflatrems, janthitrems, lolitrems, paspalitrems, penitrems, shearinines, sulpinines, and terpendoles are biogenetically related but structurally varied tremorgenic and neurotoxic mycotoxins produced by fungi. All these metabolites derive from the biosynthetic intermediate paspaline, a frequently occurring IDT on its own right. In this comprehensive review, we highlight the similarities and differences of the IDT biosynthetic pathways that lead to the generation of the main paspaline-derived IDT subgroups. We survey the taxonomic distribution and the regulation of IDT production in various fungi and compare the organization of the known IDT biosynthetic gene clusters. A detailed assessment of the highly diverse biological activities of these mycotoxins leads us to emphasize the significant losses that paspaline-derived IDTs cause in agriculture, and compels us to warn about the various hazards they represent towards human and livestock health. Conversely, we also describe the potential utility of these versatile molecules as lead compounds for pharmaceutical drug discovery, and examine the prospects for their industrial scale manufacture in genetically manipulated IDT producers or domesticated host microorganisms in synthetic biological production systems.
Topics: Biosynthetic Pathways; Diterpenes; Fungi; Humans; Indoles; Mycotoxins; Neurotoxins; Tremor
PubMed: 30613899
DOI: 10.1007/s00253-018-09594-x -
European Journal of Drug Metabolism and... Jan 2022Diterpene lactones have been identified as active compounds in several medicinal plants, including Andrographis paniculata (Burm. f.) Nees, which is a medicinal plant... (Review)
Review
Diterpene lactones have been identified as active compounds in several medicinal plants, including Andrographis paniculata (Burm. f.) Nees, which is a medicinal plant that has been used for centuries across the world. Andrographolide is the major diterpene from A. paniculata and the main bioactive constituent of this species. The effectiveness of diterpenes can be affected by factors that limit their oral bioavailability, such as their poor water solubility, slow dissolution rates, low gastrointestinal absorption, high chemical and metabolic instability, and rapid excretion. In this context, the purpose of the present review is to compile and compare literature data on the bioavailability of diterpene lactones from A. paniculata after oral administration in medicinal plant extracts or in their free forms and to highlight strategies that have been used to improve their oral bioavailability. Considering that medicinal plant extracts are commonly used as dried powder that is reconstituted in water before oral administration, novel pharmaceutical formulation strategies that are used to overcome difficulties with diterpene solubility are also compiled in this review. The use of self-microemulsifying drug delivery systems is a good strategy to enhance the dissolution and consequently the bioavailability of andrographolide after oral administration of A. paniculata extract formulations. On the other hand, herbosome technology, pH-sensitive nanoparticles, nanosuspensions, nanoemulsions, nanocrystal suspensions, nanocrystal-based solid dispersions, and solid dispersion systems are useful to formulate andrographolide in its free form and increase its oral bioavailability. The use of a suitable andrographolide delivery system is essential to achieve its therapeutic potential.
Topics: Administration, Oral; Andrographis paniculata; Biological Availability; Diterpenes; Drug Compounding; Humans; Lactones; Phytotherapy; Plant Extracts; Plants, Medicinal
PubMed: 34816382
DOI: 10.1007/s13318-021-00736-7 -
Molecules (Basel, Switzerland) Oct 2022Indole diterpenes are a large class of secondary metabolites produced by fungi, possessing a cyclic diterpenoid backbone and an indole moiety. Novel structures and... (Review)
Review
Indole diterpenes are a large class of secondary metabolites produced by fungi, possessing a cyclic diterpenoid backbone and an indole moiety. Novel structures and important biological activity have made indole diterpenes one of the focuses of synthetic chemists. Although the discovery, identification, structural diversity, biological activity and especially structure-activity relationship of indole diterpenes have been reported in some papers in recent years, they are absent of a systematic and comprehensive analysis, and there is no elucidation of enzymes related to this kind of natural product. Therefore, it is necessary to summarize the relevant reports to provide new perspectives for the following research. In this review, for the first time, the function of related synthases and the structure-activity relationship of indole diterpenes are expounded, and the recent research advances of them are emphasized.
Topics: Diterpenes; Fungi; Indoles; Biological Products
PubMed: 36296463
DOI: 10.3390/molecules27206870 -
Biomolecules Jan 2022The dried flower buds of the plant Sieb. et Zucc. have been largely used in traditional Chinese medicine for the treatment of inflammatory diseases. Numerous... (Review)
Review
The dried flower buds of the plant Sieb. et Zucc. have been largely used in traditional Chinese medicine for the treatment of inflammatory diseases. Numerous diterpenoids have been isolated from the Genkwa Flos (yuanhua in Chinese), including a series of daphnane-type diterpene designated as yuanhuacin (YC, often improperly designated as yuanhuacine) and analogues with a patronymic name. The series includes ten daphnane-type diterpenes: yuanhuacin, yuanhuadin (YD), yuanhuafin (YF), yuanhuagin (YG), yuanhuahin (YH), yuanhuajin (YJ), yuanhualin (YL), yuanhuamin (YM), yuanhuapin (YP), and yuanhuatin (YT). They are distinct from the rare flavonoid yuanhuanin. The series comprises several anticancer agents, such as the lead compound YC, which has revealed potent activity in vitro and in vivo against models of lung and breast cancers. The main signaling pathways implicated in the antitumor effects have been delineated. Protein kinase C is a key factor of activity for YC, but in general the molecular targets at the origin of the activity of these compounds remain little defined. Promising anticancer effects have been reported with analogues YD and YT, whereas compounds YF and YP are considered more toxic. The pharmacological activity of each compound is presented, as well as the properties of Genkwa Flos extracts. The potential toxic effects associated with the use of these compounds are also underlined.
Topics: Anti-Inflammatory Agents; Diterpenes; Flowers
PubMed: 35204693
DOI: 10.3390/biom12020192 -
Journal of Natural Products Jul 2022Sixteen diterpenes (-), along with 10 previously described compounds, including four flavonoids and six diterpenes, were isolated from the aerial parts of growing in... (Review)
Review
Sixteen diterpenes (-), along with 10 previously described compounds, including four flavonoids and six diterpenes, were isolated from the aerial parts of growing in Saudi Arabia. The diterpene structures were elucidated using NMR spectroscopy and mass spectrometry data. Furthermore, a DFT/NMR procedure was used to suggest the relative configuration of several compounds. The labdane-derived skeletons, namely, -atisane, -beyerene, -trachylobane, and -kaurene, were identified. The extracts, fractions, and pure compounds were then tested against , , , and . One diterpenoid, namely, psiadin, showed an additive effect with the antiseptic chlorhexidine, with a fractional inhibitory concentration index of less than 1. Additionally, psiadin showed a prospective inhibition activity for bacterial efflux pumps.
Topics: Anti-Infective Agents; Asteraceae; Diterpenes; Molecular Structure; Prospective Studies
PubMed: 35748331
DOI: 10.1021/acs.jnatprod.1c01093 -
Molecules (Basel, Switzerland) Feb 2019Steviosides, rebaudiosides and their analogues constitute a major class of naturally occurring biologically active diterpene compounds. The wide spectrum of... (Review)
Review
Steviosides, rebaudiosides and their analogues constitute a major class of naturally occurring biologically active diterpene compounds. The wide spectrum of pharmacological activity of this group of compounds has developed an interest among medicinal chemists to synthesize, purify, and analyze more selective and potent isosteviol derivatives. It has potential biological applications and improves the field of medicinal chemistry by designing novel drugs with the ability to cope against resistance developing diseases. The outstanding advancement in the design and synthesis of isosteviol and its derivative has proved its effectiveness and importance in the field of medicinal chemical research. The present review is an effort to integrate recently developed novel drugs syntheses from isosteviol and potentially active pharmacological importance of the isosteviol derivatives covering the recent advances.
Topics: Chemistry, Pharmaceutical; Diterpenes; Diterpenes, Kaurane; Drug Design; Humans; Structure-Activity Relationship
PubMed: 30769819
DOI: 10.3390/molecules24040678